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29 January 2019 Impact of Radiotherapy Concurrent with Anti-PD-1 Therapy on the Lung Tissue of Tumor-Bearing Mice
Feng Wang, Yuan Luo, Xiaoli Tian, Shijing Ma, Yingming Sun, Chengcheng You, Yan Gong, Conghua Xie
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Abstract

Pneumonitis is a common adverse effect found in non-small cell lung cancer patients after radiotherapy or immune checkpoint inhibitor treatment. We investigated the effects of these two therapies, combined, in the lung tissue of an orthotopic tumor-bearing mouse model. The mice received an 8 Gy dose three times with or without 200 µg anti-programmed death-1 (anti-PD-1) antibody intraperitoneal injection every three days. Lung tissues were H&E stained to determine histological changes. The serum levels of cytokines, such as interferon-γ, tumor necrosis factor and interleukin-5, were detected by cytometric bead array. The neutrophil infiltration was evaluated by immunohistochemical staining for myeloperoxidase. The lung injury score was higher in the treated groups than the control group, especially in the combined treatment group, in which the proportion of neutrophils in lung tissues was significantly higher compared to any other groups. Similarly, the CD4/CD8 ratio of the lung tissues in the combined treatment group, as well as the serum levels of interferon-γ, tumor necrosis factor and interleukin-5, were significantly higher than the other groups. These findings indicate that radiation combined with anti-PD-1 treatment leads to more severe lung injury in the orthotopic tumor-bearing mouse model, accompanied by increased neutrophil infiltration and increased inflammatory response.

©2019 by Radiation Research Society. All rights of reproduction in any form reserved.
Feng Wang, Yuan Luo, Xiaoli Tian, Shijing Ma, Yingming Sun, Chengcheng You, Yan Gong, and Conghua Xie "Impact of Radiotherapy Concurrent with Anti-PD-1 Therapy on the Lung Tissue of Tumor-Bearing Mice," Radiation Research 191(3), 271-277, (29 January 2019). https://doi.org/10.1667/RR15182.1
Received: 13 July 2018; Accepted: 10 January 2019; Published: 29 January 2019
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